This invention relates to pharmaceutical formulations for the intranasal administration of proteins.
It is now possible to manufacture well-defined, highly purified proteins on a large scale. This has revolutionized many areas of medicine. However, these proteins, without exception, currently have to be administered by injection because they are inadequately absorbed by the body when administered by other routes.
It would be highly desirable to administer high molecular weight proteins by a non-injected route in order to improve patient acceptability, compliance and convenience.
The nasal route has been successfully used for the administration of a number of peptide drugs. Simple aqueous solution formulations for the nasal administration of peptides including desmopressin (molecular weight 1.1 kDa), salmon calcitonin (3.5 kDa) and LHRH analogues such as nafarelin (1.3 kDa) are on the market. It should be noted, however, that the bioavailability of peptides from these formulations is generally low. For example, the reported nasal bioavailability (relative to the injection route) in humans of nafarelin and salmon calcitonin is around 3% (Martindale, The Extra Pharmacopoeia, 33rd edition, Pharmaceutical Press, London, pages 1291 and 750 (2002)).
Formulations for intranasal delivery containing selected peptide and low molecular weight protein drugs, such as insulin (molecular weight 5.8 kDa), leuprolide (1.3 kDa), goserelin (1.3 kDa), salmon calcitonin and parathyroid hormone (1-34) (4.2 kDa) have also been reported (International application publication No. WO 90/09780; Illum et al., Pharmaceutical Research, 11:1186-1189 (1994); Illum et al., STP Pharma Sciences, 10:89-94 (2000); Illum, Drug Discovery Today, 7:1184-1189 (2002); Illum, J. Control. Rel, 87:187-198 (2003); and European published patent application EP 943 326 A1).
The nasal route of delivery has not, however, proved successful for larger proteins with molecular weights in excess of 10 kDa (Rouan, Modern Pharmaceutics, 3rd Edition, Chapter 22, pp. 866-867, Banker and Rhodes (eds), Marcel Dekker, New York (1996)).
The listing or discussion of a prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.
There remains a need for alternative means for the delivery of proteins having a molecular weight of 10 kDa or greater.